Information obtained by retrospective analysis of cases not initially managed to provide quality data is of limited use in forming a basis for valid conclusions. This research group, through the use of the prospective randomized clinical trial is attempting to apply the scientific method to the solution of clinical problems in primary breast cancer. As a participating institution in the NSABP we have contributed, and are continuing to contribute data from patients entered into the various group protocols. We have made a major contribution to Protocol 4, a comparison of radical mastectomy versus total mastectomy with radiation vs. total mastectomy alone. As follow-up data continued to indicate the validity of the original hypothesis that there was no significant influence of treatment on disease-free interval or survival, a second surgical prospective trial was undertaken to evaluate segmental mastectomy with and without breast radiation vs. total mastectomy. All patients with positive axillary nodes receive a standard 2 drug chemotherapy. Patients have also been entered into adjuvant chemotherapy protocols, specifically Protocol No.5: L-PAM vs. Placebo; No.7: L-PAM vs. L-PAM and 5FU; No.8: L-PAM and 5FU vs. L-PAM, 5FU and Methotrexate; No.10: L-PAM and 5FU vs. L-PAM, 5FU and C. parvum, No.9: L-PAM and 5FU vs. L-PAM, 5FU and Tamoxifen. Thus, data will be obtained prospectively to evaluate the efficacy of 1 vs. 2 vs. 3 drugs involving chemo, hormonal and immunotherapeutic combinations giving information on the value and toxicity of multi-modality combination therapy. This application renewal seeks funding to a) permit continued patient accrual in ongoing protocols, b) to continue follow-up of patients already entered, and c) to collect pertinent biological material and information relevant to such protocols. The aim of this proposal is to continue to develop these kinds of data, enhancing the multi-disciplinary approach of this institution through clinical trials to obtain meaningful information in planning the primary therapy of breast cancer.